ABSTRACT
Clioquinol (5-chloro-7-iodoquinolin-8-ol or ICHQ) was recently showed to presents an in vitro effective antileishmanial action, causing changes in membrane permeability, mitochondrial functionality, and parasite morphology. In the present study, ICHQ was incorporated into a Poloxamer 407-based polymeric micelles system (ICHQ/M), and its antileishmanial activity was in vivo evaluated in L. amazonensis-infected BALB/c mice. Amphotericin B (AmpB) and its liposomal formulation (Ambisome®) were used as controls. Parasitological and immunological evaluations were performed 30â¯days after the treatment. Results indicated more significant reductions in the average lesion diameter and parasite burden in ICHQ or ICHQ/M-treated mice, which were associated with the development of a polarized Th1 immune response, based on production of high levels of IFN-γ, IL-12, TNF-α, GM-CSF, and antileishmanial IgG2a antibody. Control groups´ mice produced high levels of IL-4, IL-10, and IgG1 isotype antibody. No organic toxicity was found by using ICHQ or ICHQ/M to treat the animals, although those receiving AmpB and Ambisome® have presented higher levels of renal and hepatic damage markers. In conclusion, results suggested that the ICHQ/M composition can be considered as an antileishmanial candidate to be tested against human leishmaniasis.
Subject(s)
Antiprotozoal Agents/immunology , Antiprotozoal Agents/therapeutic use , Clioquinol/immunology , Clioquinol/therapeutic use , Leishmania mexicana/drug effects , Leishmaniasis, Visceral/drug therapy , Poloxamer/administration & dosage , Amphotericin B/administration & dosage , Amphotericin B/therapeutic use , Amphotericin B/toxicity , Animals , Antibodies, Protozoan/blood , Antigens, Protozoan/administration & dosage , Antigens, Protozoan/immunology , Antigens, Protozoan/therapeutic use , Antiprotozoal Agents/administration & dosage , Antiprotozoal Agents/toxicity , Clioquinol/administration & dosage , Cytokines/biosynthesis , Cytokines/immunology , Drug Delivery Systems/methods , Humans , Immunoglobulin G/blood , Interferon-gamma/biosynthesis , Interferon-gamma/immunology , Leishmania mexicana/growth & development , Leishmaniasis, Visceral/immunology , Mice , Mice, Inbred BALB C , Micelles , Parasite Load , Poloxamer/chemistry , Th1 CellsABSTRACT
Ten patients with positive patch test reactions to clioquinol were retested in 1979 after an average interval of 6 years. On subsequent testing we also examined test reactions to other quinoline derivatives (including antimalarial drugs) and potassium iodide. All patients showed a positive reaction to clioquinol at retesting. Many cross-reactions of hydroxyquinolines included reactions to quinoline-based antimalarial drugs, and a few allergic reactions to potassium iodide. The consequences of these findings are discussed.
Subject(s)
Clioquinol/immunology , Cross Reactions , Dermatitis, Atopic/etiology , Quinolines/adverse effects , Adult , Aged , Antimalarials/adverse effects , Clioquinol/adverse effects , Dermatitis, Atopic/immunology , Drug Hypersensitivity/etiology , Drug Hypersensitivity/immunology , Female , Humans , Male , Middle Aged , Patch Tests , Potassium Iodide/adverse effectsABSTRACT
Antibody to clioquinol(5-chloro-7-iodo-8-hydroxyquinoline:CIHQ) was detected by passive hemagglutinating reaction in rabbits receiving a prolonged administration of Emaform which was once a commercial preparation of CIHQ. The antibody was shown to be in the immunoglobulin fractions by separation with a specific immunoadsorbent, and it had relatively broad antigenic specificity. The antibody was also demonstrated in sera from patients who suffered from Subacute Myelo-Optico-Neuropathy (SMON) and from normal healthy individuals. However, its titer and frequency of positive reactors in the former were higher than those in the latter, and the two groups could be differentiated each other in frequency distribution patterns of the antibody proprietors. From these results, we discussed on desirable application of sero-epidemiological study to assessment of effects of chemical pollutants on living systems.
Subject(s)
Antibodies/analysis , Clioquinol/immunology , Myelitis/immunology , Optic Neuritis/immunology , Adult , Aged , Animals , Antibody Specificity , Hemagglutination Inhibition Tests , Hemagglutination Tests , Humans , Immunoglobulins/analysis , Infant , Rabbits/immunology , SyndromeABSTRACT
Twenty-one patients with fixed drug eruption were studied with the lymphocyte transformation test. In no patient was there blast transformation when the responsible drug (1:10,000 dilution) was added to the lymphocyte culture. The addition to the lymphocyte culture of 0.4 ml of autologous serum, taken at the acme of the clinical reaction, produced blast transformation of the lymphocytes, and when the responsible drug (1:10,000 dilution) was added to this system, blast transformation increased by several times. The addition of the responsible drug to autologous serum obtained during clinical remission produced a minimal or negative response. These findings suggest that during fixed drug eruptions a blast transforming factor appears temporarily in the serum and increases its activity in the presence of the responsible drug. This factor spontaneously diminishes or disappears a few days after clinical exacerbation.
